The Role of Bifidobacterium in COVID-19: A Systematic Review
Clarissa Reginato Taufer, Pabulo Henrique Rampelotto
Life, doi:10.3390/life13091847
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, mainly causes respiratory and intestinal symptoms and changes in the microbiota of patients. We performed a systematic search in major databases using "Bifidobacterium" and "COVID-19" or "SARS-CoV-2" as key terms to assess the relationship of the genus to COVID-19. After the selection steps, 25 articles were analyzed. Of these, eighteen were observational, and seven were interventional articles that evaluated the use of Bifidobacterium alone or in mix as probiotics for additional treatment of patients with COVID-19. All stages and severities were contemplated, including post-COVID-19 patients. Overall, Bifidobacterium was associated with both protective effects and reduced abundance in relation to the disease. The genus has been found to be abundant in some cases and linked to disease severity. The studies evaluating the use of Bifidobacterium as probiotics have demonstrated the potential of this genus in reducing symptoms, improving pulmonary function, reducing inflammatory markers, alleviating gastrointestinal symptoms, and even contributing to better control of mortality. In summary, Bifidobacterium may offer protection against COVID-19 through its ability to modulate the immune response, reduce inflammation, compete with pathogenic microbes, and maintain gut barrier function. The findings provide valuable insights into the relationship between the disease and the genus Bifidobacterium, highlighting the potential of microbiota modulation in the treatment of COVID-19.
Author Contributions: C.R.T.: Data collection and analysis, writing (original draft). P.H.R.: Conceptualization, supervision, analysis of results, and writing (revision). All authors have read and agreed to the published version of the manuscript. Funding: C.R.T. is the recipient of a CAPES grant (nº 88887.513461/2020-00). P.H.R. is the recipient of a CAPES grant (nº 88887.798411/2022-00). Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable.
References
Albrich, Ghosh, Ahearn-Ford, Mikaeloff, Lunjani et al., A High-Risk Gut Microbiota Configuration Associates with Fatal Hyperinflammatory Immune and Metabolic Responses to SARS-CoV-2, Gut Microbes,
doi:10.1080/19490976.2022.2073131Alessandri, Ossiprandi, Macsharry, Van Sinderen, Ventura, Bifidobacterial Dialogue With Its Human Host and Consequent Modulation of the Immune System, Front. Immunol,
doi:10.3389/fimmu.2019.02348Alessandri, Van Sinderen, Ventura, The Genus Bifidobacterium: From Genomics to Functionality of an Important Component of the Mammalian Gut Microbiota, Comput. Struct. Biotechnol. J,
doi:10.1016/j.csbj.2021.03.006Ceccarelli, Borrazzo, Pinacchio, Santinelli, Innocenti et al., Oral Bacteriotherapy in Patients With COVID-19: A Retrospective Cohort Study, Front. Nutr,
doi:10.3389/fnut.2020.613928Cui, Rao, Zeng, Wang, Ren et al., Characterization of Oral and Gut Microbiome and Plasma Metabolomics in COVID-19 Patients after 1-Year Follow-Up, Mil. Med. Res,
doi:10.1186/s40779-022-00387-yDe Vrese, Winkler, Rautenberg, Harder, Noah et al., Effect of Lactobacillus Gasseri PA 16/8, Bifidobacterium Longum SP 07/3, B. bifidum MF 20/5 on Common Cold Episodes: A Double Blind, Randomized, Controlled Trial, Clin. Nutr,
doi:10.1016/j.clnu.2005.02.006Erdo Ǧan, Tanyeri, Torun, Gönüllü, Arslan et al., The Comparition of the Efficacy of Two Different Probiotics in Rotavirus Gastroenteritis in Children, J. Trop. Med,
doi:10.1155/2012/787240Ettorre, Ceccarelli, Marazzato, Campagna, Pinacchio et al., Challenges in the Management of SARS-CoV2 Infection: The Role of Oral Bacteriotherapy as Complementary Therapeutic Strategy to Avoid the Progression of COVID-19, Front. Med,
doi:10.3389/fmed.2020.00389Ewaschuk, Diaz, Meddings, Diederichs, Dmytrash et al., Secreted Bioactive Factors from Bifidobacterium Infantis Enhance Epithelial Cell Barrier Function, Am. J. Physiol. Gastrointest. Liver Physiol,
doi:10.1152/ajpgi.90227.2008Fattahi, Heidari, Khosroushahi, Review of Short-Chain Fatty Acids Effects on the Immune System and Cancer, Food Biosci,
doi:10.1016/j.fbio.2020.100793Ferreira-Junior, Borgonovi, De Salis, Leite, Dantas et al., Detection of Intestinal Dysbiosis in Post-COVID-19 Patients One to Eight Months after Acute Disease Resolution, Int. J. Environ. Res. Public Health,
doi:10.3390/ijerph191610189Fujiwara, Hashiba, Hirota, Forstner, Proteinaceous Factor(s) in Culture Supernatant Fluids of Bifidobacteria Which Prevents the Binding of Enterotoxigenic Escherichia Coli to Gangliotetraosylceramide, Appl. Environ. Microbiol,
doi:10.1128/aem.63.2.506-512.1997Gopal, Prasad, Smart, Gill, In Vitro Adherence Properties of Lactobacillus Rhamnosus DR20 and Bifidobacterium Lactis DR10 Strains and Their Antagonistic Activity against an Enterotoxigenic Escherichia Coli, Int. J. Food Microbiol,
doi:10.1016/S0168-1605(01)00440-8Groeger, Schiavi, Grant, Kurnik-Łucka, Michalovich et al., Intranasal Bifidobacterium Longum Protects against Viral-Induced Lung Inflammation and Injury in a Murine Model of Lethal Influenza Infection, eBioMedicine,
doi:10.1016/j.ebiom.2020.102981Gumenyuk, Golod, Silaeva, Sorokina, Ilyasov et al., Gut Microbiota Alterations and Their Relationship To the Disease Severity and Some Cytokine Profile Indicators in Patients With COVID-19, Bull. Russ. State Med. Univ,
doi:10.24075/brsmu.2022.006Hazan, Stollman, Bozkurt, Dave, Papoutsis et al., Lost Microbes of COVID-19: Bifidobacterium, Faecalibacterium Depletion and Decreased Microbiome Diversity Associated with SARS-CoV-2 Infection Severity, BMJ Open Gastroenterol,
doi:10.1136/bmjgast-2022-000871Islam, Foysal, Hoque, Mehedi, Rob et al., Dysbiosis of Oral and Gut Microbiomes in SARS-CoV-2 Infected Patients in Bangladesh: Elucidating the Role of Opportunistic Gut Microbes, Front. Med,
doi:10.3389/fmed.2022.821777Ivashkin, Fomin, Moiseev, Brovko, Maslennikov et al., Efficacy of a Probiotic Consisting of Lacticaseibacillus Rhamnosus PDV 1705, Bifidobacterium Bifidum PDV 0903, Bifidobacterium Longum Subsp. Infantis PDV 1911, and Bifidobacterium Longum Subsp. Longum PDV 2301 in the Treatment of Hospitalized Patients Wit, Probiotics Antimicrob. Proteins,
doi:10.1007/s12602-021-09858-5Kawahara, Takahashi, Oishi, Tanaka, Masuda et al., Consecutive Oral Administration of Bifidobacterium Longum MM-2 Improves the Defense System against Influenza Virus Infection by Enhancing Natural Killer Cell Activity in a Murine Model, Microbiol. Immunol,
doi:10.1111/1348-0421.12210Kim, Zhang, Rauseo, Goss, Mudd et al., The Salivary and Nasopharyngeal Microbiomes Are Associated with SARS-CoV-2 Infection and Disease Severity, J. Med. Virol,
doi:10.1002/jmv.28445Laterza, Putignani, Settanni, Petito, Varca et al., Ecology and Machine Learning-Based Classification Models of Gut Microbiota and Inflammatory Markers May Evaluate the Effects of Probiotic Supplementation in Patients Recently Recovered from COVID-19, Int. J. Mol. Sci,
doi:10.3390/ijms24076623Leyer, Li, Mubasher, Reifer, Ouwehand, Probiotic Effects on Cold and Influenza-like Symptom Incidence and Duration in Children, Pediatrics,
doi:10.1542/peds.2008-2666Li, Cheng, Xu, Su, Cai et al., The Role of Probiotics in Coronavirus Disease-19 Infection in Wuhan: A Retrospective Study of 311 Severe Patients, Int. Immunopharmacol,
doi:10.1016/j.intimp.2021.107531Li, Yang, Zhou, Disoma, Dong et al., Microbiome Profiling Using Shotgun Metagenomic Sequencing Identified Unique Microorganisms in COVID-19 Patients with Altered Gut Microbiota, Front. Microbiol,
doi:10.3389/fmicb.2021.712081Lievin, Peiffer, Hudault, Rochat, Brassart et al., Bifidobacterium Strains from Resident Infant Human Gastrointestinal Microflora Exert Antimicrobial Activity, Gut,
doi:10.1136/gut.47.5.646Liu, Mak, Su, Yeoh, Lui et al., Gut Microbiota Dynamics in a Prospective Cohort of Patients with Post-Acute COVID-19 Syndrome, Gut,
doi:10.1136/gutjnl-2021-325989Liu, Zhang, Dong, Guo, Adhesion and Immunomodulatory Effects of Bifidobacterium Lactis HN019 on Intestinal Epithelial Cells INT-407, World J. Gastroenterol,
doi:10.3748/wjg.v16.i18.2283Lu, Fang, Liu, Li, Zhang et al., The Potential Role of Probiotics in Protection against Influenza a Virus Infection in Mice, Foods,
doi:10.3390/foods10040902Maddah, Goodarzi, Asadi-Yousefabad, Abbasluo, Shariati et al., Evaluation of the Gut Microbiome Associated with COVID-19, Inform. Med. Unlocked,
doi:10.1016/j.imu.2023.101239Mahooti, Abdolalipour, Salehzadeh, Mohebbi, Gorji et al., Immunomodulatory and Prophylactic Effects of Bifidobacterium Bifidum Probiotic Strain on Influenza Infection in Mice, World J. Microbiol. Biotechnol,
doi:10.1007/s11274-019-2667-0Marfia, Navone, Guarnaccia, Campanella, Mondoni et al., Decreased Serum Level of Sphingosine-1-phosphate: A Novel Predictor of Clinical Severity in COVID-19, EMBO Mol. Med,
doi:10.15252/emmm.202013424Mazzarelli, Giancola, Fontana, Piselli, Binda et al., Gut Microbiota Composition in COVID-19 Hospitalized Patients with Mild or Severe Symptoms, Front. Microbiol,
doi:10.3389/fmicb.2022.1049215Mirzayi, Renson, Furlanello, Sansone, Zohra et al., Reporting Guidelines for Human Microbiome Research: The STORMS Checklist, Nat. Med,
doi:10.1038/s41591-021-01552-xMoola, Munn, Tufanaru, Aromataris, Sears et al., Chapter 7: Systematic Reviews of Etiology and Risk
Page, Mckenzie, Bossuyt, Boutron, Hoffmann et al., The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews, BMJ,
doi:10.1136/bmj.n71Qin, Zheng, Yao, Guo, Zuo et al., Influence of H7N9 Virus Infection and Associated Treatment on Human Gut Microbiota, Sci. Rep,
doi:10.1038/srep14771Reinold, Farahpour, Fehring, Dolff, Konik et al., A Pro-Inflammatory Gut Microbiome Characterizes SARS-CoV-2 Infected Patients and a Reduction in the Connectivity of an Anti-Inflammatory Bacterial Network Associates With Severe COVID-19, Front. Cell. Infect. Microbiol,
doi:10.3389/fcimb.2021.747816Romani, Del Chierico, Macari, Pane, Ristori et al., The Relationship Between Pediatric Gut Microbiota and SARS-CoV-2 Infection, Front. Cell. Infect. Microbiol,
doi:10.3389/fcimb.2022.908492Rueca, Fontana, Bartolini, Piselli, Mazzarelli et al., Investigation of Nasal/Oropharyngeal Microbial Community of COVID-19 Patients by 16S RDNA Sequencing, Int. J. Environ. Res. Public Health,
doi:10.3390/ijerph18042174Saviano, Potenza, Siciliano, Petruzziello, Tarli et al., COVID-19 Pneumonia and Gut Inflammation: The Role of a Mix of Three Probiotic Strains in Reducing Inflammatory Markers and Need for Oxygen Support, J. Clin. Med,
doi:10.3390/jcm11133758Segal, Mak, Mullish, Alexander, Ng et al., The Gut Microbiome: An under-Recognised Contributor to the COVID-19 Pandemic?, Therap. Adv. Gastroenterol,
doi:10.1177/1756284820974914Sgorbati, Biavati, Palenzona, The Genus Bifidobacterium
Sterne, Hernán, Reeves, Savović, Berkman et al., A Tool for Assessing Risk of Bias in Non-Randomised Studies of Interventions, BMJ,
doi:10.1136/bmj.i4919Sterne, Savović, Page, Elbers, Blencowe et al., RoB 2: A Revised Tool for Assessing Risk of Bias in Randomised Trials, BMJ,
doi:10.1136/bmj.l4898Sun, Song, Liu, Tan, Lin et al., Gut Microbiome Alterations and Gut Barrier Dysfunction Are Associated with Host Immune Homeostasis in COVID-19 Patients, BMC Med,
doi:10.1186/s12916-021-02212-0Suskun, Kilic, Yilmaz Ciftdogan, Guven, Karbuz et al., Intestinal Microbiota Composition of Children with Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Multisystem Inflammatory Syndrome (MIS-C), Eur. J. Pediatr,
doi:10.1007/s00431-022-04494-9Tojo, Suárez, Clemente, De, Reyes-Gavilán et al., Intestinal Microbiota in Health and Disease: Role of Bifidobacteria in Gut Homeostasis, World J. Gastroenterol,
doi:10.3748/wjg.v20.i41.15163Turroni, Bifidobacteria: From Ecology to Genomics, Front. Biosci,
doi:10.2741/3559Usta-Gorgun, Yilmaz-Ersan, Short-Chain Fatty Acids Production by Bifidobacterium Species in the Presence of Salep, Electron. J. Biotechnol,
doi:10.1016/j.ejbt.2020.06.004Wang, Usyk, Sollecito, Qiu, Williams-Nguyen et al., Altered Gut Microbiota and Host Metabolite Profiles in Women with Human Immunodeficiency Virus, Clin. Infect. Dis,
doi:10.1093/cid/ciz1117Wang, Xiao, Yao, Guo, Lu et al., The Role of Bifidobacteria in Gut Barrier Function after Thermal Injury in Rats, J. Trauma Inj. Infect. Crit. Care,
doi:10.1097/01.ta.0000196574.70614.27Wang, Zhou, Lu, Hu, Xiao et al., Altered Gut Microbiota Composition in Children and Their Caregivers Infected with the SARS-CoV-2 Omicron Variant, World J. Pediatr,
doi:10.1007/s12519-022-00659-6Yan, Yang, Ross, Stanton, Zhang et al., Bifidobacterium Longum Subsp. Longum YS108R Fermented Milk Alleviates DSS Induced Colitis via Anti-Inflammation, Mucosal Barrier Maintenance and Gut Microbiota Modulation, J. Funct. Foods,
doi:10.1016/j.jff.2020.104153Yao, Zhao, Wang, Liu, Bifidobacterium Longum: Protection against Inflammatory Bowel Disease, J. Immunol. Res,
doi:10.1155/2021/8030297Yasui, Kiyoshima, Hori, Shida, Protection against Influenza Virus Infection of Mice Fed Bifidobacterium Breve YIT4064, Clin. Diagn. Lab. Immunol,
doi:10.1128/CDLI.6.2.186-192.1999Yeoh, Zuo, Lui, Zhang, Liu et al., Gut Microbiota Composition Reflects Disease Severity and Dysfunctional Immune Responses in Patients with COVID-19, Gut,
doi:10.1136/gutjnl-2020-323020Yitbarek, Weese, Alkie, Parkinson, Sharif, Influenza A Virus Subtype H9N2 Infection Disrupts the Composition of Intestinal Microbiota of Chickens, FEMS Microbiol. Ecol,
doi:10.1093/femsec/fix165Zhang, Hu, Feng, Hu, Wang et al., Influenza Infection Elicits an Expansion of Gut Population of Endogenous Bifidobacterium Animalis Which Protects Mice against Infection, Genome Biol,
doi:10.1186/s13059-020-02007-1
